The objectives of this program are to gain insight into the molecular mechanisms involved in synapse formation and function. To this end we have developed a procedure for the isolation of synaptic complexes (pre- and post-synaptic membranes in contact) in a highly purified form. The method utilized CsCl density gradients and zonal centrifugation. Our earlier studies of synaptogenesis in the intact cerebellar cortices of monkey and pig permitted the recovery and analysis of relatively homogeneous synaptic populations. These preparations will be used for the following studies: 1) isolation from and characterization of macromolecules in the synaptic complex which may be involved in cell- cell recognition; 2) investigation of the properties of receptor molecules in the synaptic membrane which bind transmitters or pharmacologically active drugs; 3) comparison of the biochemical properties of synaptic complexes isolated from pathological tissue with those of synapses isolated from normal tissue.